Thompson, Reid

Abstract BACKGROUND Standard of care (SOC) and patient survival in glioblastoma have changed little in the past 17 years. We evaluated in a phase 3 trial whether adding an autologous tumor lysate-loaded dendritic cell vaccine (murcidencel) to SOC extends survival. Patients and METHODS Newly diagnosed glioblastoma patients were randomized 2:1 to either murcidencel or placebo. Under a crossover design, all patients could receive murcidencel following tumor recurrence. All parties remained blinded regarding treatments before recurrence. Patients thus received murcidencel at new diagnosis (nGBM) or at recurrence (rGBM) following crossover from placebo. The primary and secondary endpoints compare overall survival (OS) with contemporaneous, matched external controls. Four sets of analyses were conducted to ensure rigorous matching of the controls, reduce biases, and confirm the robustness of the results. RESULTS 331 patients were enrolled. With the crossover, 89% received murcidencel. Median OS (mOS) for nGBM patients (n = 232) was 19.3 months from randomization (22.4 months from surgery) with murcidencel vs. 16.5 months from randomization in the controls (HR = 0.80, p = 0.002). Survival at 48 months from randomization was 15.7% vs. 9.9%, and at 60 months was 13% vs. 5.7%. For rGBM (n = 64), mOS was 13.2 months from relapse vs. 7.8 months in the controls (HR = 0.58, p < 0.001). Survival at 24 months post-recurrence was 20.7% vs. 9.6%, and at 30 months post-recurrence was 11.1% vs 5.1%. In nGBM patients with methylated MGMT (n = 90), mOS was 30.2 months from randomization (33 months from surgery) with murcidencel vs. 21.3 months from randomization in the controls (HR = 0.74, p = 0.027). The treatment was well tolerated, with only 5 serious adverse events deemed at least possibly related to the vaccine. CONCLUSION Clinically meaningful and statistically significant survival extension was seen in both nGBM and rGBM patients treated with murcidencel and SOC compared with contemporaneous, matched external controls who received SOC alone.

Objective: To characterize the risk of progression to nonserviceable hearing in patients with sporadic vestibular schwannomas (VS) who elect initial observation. Study Design: Retrospective case series. Setting: Two tertiary care centers. Patients: VS patients with serviceable hearing who underwent at least two audiograms and two MRI studies before intervention or loss to follow-up. Main outcome measure(s): Serviceable hearing, defined as the pure tone average ≤ 50 dB HL and word recognition score ≥ 50%. Results: Four-hundred sixty-six patients (median age of 57 yr and median tumor diameter of 7.3 mm) had serviceable hearing at presentation and were followed for a median of 2.3 years (IQR 1.0 – 4.0). Kaplan–Meier estimated rates of maintaining serviceable hearing (95% CI; number still at risk) at 1, 3, 5, 7, and 10 years following diagnosis were 94% (91–96; 357), 77% (73–82; 172), 66% (60–73; 81), 56% (49–65; 31), and 44% (33–59; 10), respectively. Each 10-dB increase in pure-tone averages at diagnosis was associated with a 2-fold increased likelihood of developing nonserviceable hearing (hazard ratio 2.07; p < 0.001). Each 10% decrease in word recognition score was associated with a 1.5-fold increased likelihood of developing nonserviceable hearing (hazard ratio 1.48; p < 0.001). Conclusions: Among patients with sporadic VS, good baseline word recognition score and low pure-tone average are jointly associated with maintenance of serviceable hearing. These data may be used to guide patient counseling and optimize management.